The Department of Health (DH) today (February 27) drew the public’s attention to the decision of the Pharmacy and Poisons (Registration of Pharmaceutical Products and Substances: Certification of Clinical Trial/Medicinal Test) Committee (the Registration Committee) of the Pharmacy and Poisons Board to deregister oral pharmaceutical products containing ketoconazole with effect from July 1, 2014, because the benefits of the products no longer outweigh their risks.

The Registration Committee’s decision was made at its meeting yesterday (February 26) after taking into consideration the findings from the review conducted by the European Medicines Agency’s Committee on Medicinal Products for Human Use, decisions by overseas drug regulatory agencies, and the use of the products in Hong Kong.

Ketoconazole is an anti-fungal agent used orally or topically. It is given orally in chronic mucocutaneous or vaginal candidiasis, fungal infections of the gastrointestinal tract, dermatophyte infections of the skin and fingernails not responding to topical treatment, and systemic fungal infections.

The European Medicines Agency concluded that the incidence and seriousness of liver injury with oral ketoconazole were higher than with other antifungals. In light of the increased rate of liver injury and the availability of alternative anti-fungal treatments, the European Medicines Agency concluded that the benefits did not outweigh the risks and recommended suspending oral ketoconazole throughout the European Union. Topical formulations of ketoconazole (such as creams, gels, shampoos and topical solutions) could continue to be used as the amount absorbed throughout the body surface is very low with these formulations.

In Hong Kong, there are currently 21 registered oral pharmaceutical products containing ketoconazole, marketed by 17 manufacturers and wholesalers. They are all prescription-only medicines which can only be sold by pharmacies under the supervision of registered pharmacists upon doctors’ prescription. The products are listed in the Attachment.

Ketoconazole is sold commercially as a tablet for oral administration, and in a variety of formulations, such as creams and shampoos, for topical administration.

According to local clinical experts in infectious diseases, dermatology and oncology, the use of oral ketoconazole in clinical practice has almost been completely replaced by alternative anti-fungal agents. The DH will issue letters to health-care professionals to inform them of the Registration Committee’s decision to deregister oral pharmaceutical products containing ketoconazole, and to advise them to arrange suitable alternative treatments for their patients.

“When the Registration Committee’s decision takes effect on July 1, 2014, all drug manufacturers, wholesalers, retailers and health-care professionals must stop selling or supplying oral pharmaceutical products containing ketoconazole. Drug manufacturers and wholesalers are also required to recall all products concerned from the market by June 30, 2014. The DH will take enforcement action against any illegal possession or sale of such products afterwards,” a DH spokesman said.

Under the Pharmacy and Poisons Ordinance (Cap 138), illegal sale or possession for the purpose of sale of unregistered pharmaceutical products are both criminal offences. The maximum penalty for each offence is a fine of $100,000 and two years’ imprisonment.

“Doctors and pharmacies should stop prescribing or dispensing oral ketoconazole products. Patients taking oral ketoconazole products are advised to consult their health-care professionals to review their treatment plans as soon as possible,” the spokesman advised.